Comments on the article “Clinical and radiological outcomes of fixed- versus mobile-bearing total knee replacement: a meta-analysis”

Diagnosis and treatment of bone and soft tissue tumour

Management of Febrile Neutropenia - a German Prospective Hospital Cost Analysis in Lymphoproliferative Disorders, Non-Small Cell Lung Cancer, and Primary Breast Cancer

Background: Febrile neutropenia/leukopenia (FN/FL) is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy, but German data on economic consequences are limited. Patients and Methods: A prospective, multicentre, longitudinal, observational study was carried out to evaluate the occurrence of FN/FL and its impact on health resource utilization and costs in non-small cell lung cancer (NSCLC), lymphoproliferative disorder (LPD), and primary breast cancer (PBC) patients. Costs are presented from a hospital perspective. Results: A total of 325 consecutive patients (47% LPD, 37% NSCLC, 16% PBC; 46% women; 38% age >= 65 years) with 68 FN/FL episodes were evaluated. FN/FL occurred in 22% of the LPD patients, 8% of the NSCLC patients, and 27% of the PBC patients. 55 FN/FL episodes were associated with at least 1 hospital stay (LPD n = 34, NSCLC n = 10, PBC n = 11). Mean (median) cost per FN/FL episode requiring hospital care amounted to (sic) 3,950 ((sic) 2,355) and varied between (sic) 4,808 ((sic) 3,056) for LPD, (sic) 3,627 ((sic) 2,255) for NSCLC, and (sic) 1,827 ((sic) 1,969) for PBC patients. 12 FN/FL episodes (LPD n = 9, NSCLC n = 3) accounted for 60% of the total expenses. Main cost drivers were hospitalization and drugs (60 and 19% of the total costs). Conclusions: FN/FL treatment has economic relevance for hospitals. Costs vary between tumour types, being significantly higher for LPD compared to PBC patients. The impact of clinical characteristics on asymmetrically distributed costs needs further evaluation

Physicians Infrequently Adhere to Hepatitis Vaccination Guidelines for Chronic Liver Disease

Background and Goals:Hepatitis A (HAV) and hepatitis B (HBV) vaccination in patients with chronic liver disease is an accepted standard of care. We determined HAV and HBV vaccination rates in a tertiary care referral hepatology clinic and the impact of electronic health record (EHR)-based reminders on adherence to vaccination guidelines.Methods:We reviewed the records of 705 patients with chronic liver disease referred to our liver clinic in 2008 with at least two follow-up visits during the subsequent year. Demographics, referral source, etiology, and hepatitis serology were recorded. We determined whether eligible patients were offered vaccination and whether patients received vaccination. Barriers to vaccination were determined by a follow-up telephone interview.Results:HAV and HBV serologic testing prior to referral and at the liver clinic were performed in 14.5% and 17.7%; and 76.7% and 74% patients, respectively. Hepatologists recommended vaccination for HAV in 63% and for HBV in 59.7% of eligible patients. Patient demographics or disease etiology did not influence recommendation rates. Significant variability was observed in vaccination recommendation amongst individual providers (30-98.6%), which did not correlate with the number of patients seen by each physician. Vaccination recommendation rates were not different for Medicare patients with hepatitis C infection for whom a vaccination reminder was automatically generated by the EHR. Most patients who failed to get vaccination after recommendation offered no specific reason for noncompliance; insurance was a barrier in a minority.Conclusions:Hepatitis vaccination rates were suboptimal even in an academic, sub-speciality setting, with wide-variability in provider adherence to vaccination guidelines. © 2013 Thudi et al

Retention of the posterior cruciate ligament versus the posterior stabilized design in total knee arthroplasty: a prospective randomized controlled clinical trial

Background: Prosthetic design for the use in primary total knee arthroplasty has evolved into designs that preserve the posterior cruciate ligament (PCL) and those in which the ligament is routinely sacrificed (posterior stabilized). In patients with a functional PCL the decision which design is chosen depends largely on the favour and training of the surgeon. The objective of this study is to determine whether the patient's perceived outcome and speed of recovery differs between a posterior cruciate retaining total knee arthroplasty and a posterior stabilized total knee arthroplasty. Methods/Design: A randomized controlled trial will be conducted. Patients who are admitted for primary unilateral TKA due to primary osteoarthrosis are included when the following inclusion criteria are met: non-fixed fixed varus or valgus deformity less than 10 degrees, age between 55 and 85 years, body mass index less than 35 kg/m(2) and ASA score (American Society of Anaesthesiologists) I or II. Patients are randomized in 2 groups. Patients in the posterior cruciate retaining group will receive a prosthesis with a posterior cut-out for the posterior cruciate ligament and relatively flat topography. In patients allocated to the posterior stabilized group, in which the posterior cruciate ligament is excised, the design may substitute for this function by an intercondylar tibial prominence that articulates with the femur in flexion. Measurements will take place preoperatively and 6 weeks, 3 months, 6 months and 1 year postoperatively. At all measurement points patient's perceived outcome will be assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures are quality of life (SF-36) and physician reported functional status and range of motion as determined with the Knee Society Clinical Rating System (KSS). Discussion: In the current practice both posterior cruciate retaining and posterior stabilized designs for total knee arthroplasty are being used. To date no studies have been performed determining whether there is a difference in patient's perceived outcome between the two designs. Additionally, there is a lack of studies determining the speed of recovery in both designs as most studies only determine the final outcome. This randomised controlled study has been designed to determine whether the patient's perceived outcome and speed of recovery differs between a posterior cruciate retaining total knee arthroplasty and a posterior stabilized total knee arthroplasty

The pathology of familial breast cancer: The pre-BRCA1/BRCA2 era - historical perspectives

A proportion of breast carcinomas develop as a result of a genetic predispostion to the disease. Prior to cloning of the BRCA1 and BRCA2 genes a limited number of studies were carried out to identify specific histopathological characteristics of hereditary breast cancer. These studies are the subject of this review. The main finding was the association of the (atypical) medullary type of breast cancer with a family history; the most important caveat being that medullary breast cancer is found more frequently in young patients. In view of the frequent bilateral occurrence of lobular cancer, this histologic type is also likely to be associated with a predisposing genetic defect. Future investigations will have to test this hypothesis. In addition to mutations in the BRCA1 and BRCA2 genes, there are as yet unidentified genetic defects predisposing to breast cancer development, and histopathology may well help in identifying these genes in the future

Cytokines Elevated in HIV Elite Controllers Reduce HIV Replication In Vitro and Modulate HIV Restriction Factor Expression

A subset of HIV-infected individuals termed elite controllers (ECs) maintain CD4+ T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or from those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 ECs, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers [NCs]), and 48 HIV-uninfected (NEG) subjects. Four cytokines were elevated in ECs but not NCs or ART subjects: CCL14, CCL21, CCL27, and XCL1. In addition, median stromal cell-derived factor-1 (SDF-1) levels were 43% higher in ECs than in NCs. The combination of the five cytokines suppressed R5 and X4 virus replication in resting CD4+ T cells, and individually SDF-1β, CCL14, and CCL27 suppressed R5 virus replication, while SDF-1β, CCL21, and CCL14 suppressed X4 virus replication. Functional studies revealed that the combination of the five cytokines upregulated CD69 and CCR5 and downregulated CXCR4 and CCR7 on CD4+ T cells. The CD69 and CXCR4 effects were driven by SDF-1, while CCL21 downregulated CCR7. The combination of the EC-associated cytokines induced expression of the anti-HIV host restriction factors IFITM1 and IFITM2 and suppressed expression of RNase L and SAMHD1. These results identify a set of cytokines that are elevated in ECs and define their effects on cellular activation, HIV coreceptor expression, and innate restriction factor expression. This cytokine pattern may be a signature characteristic of HIV-1 elite control, potentially important for HIV therapeutic and curative strategies.IMPORTANCE Approximately 1% of people infected with HIV control virus replication without taking antiviral medications. These subjects, termed elite controllers (ECs), are known to have stronger immune responses targeting HIV than the typical HIV-infected subject, but the exact mechanisms of how their immune responses control infection are not known. In this study, we identified five soluble immune signaling molecules (cytokines) in the blood that were higher in ECs than in subjects with typical chronic HIV infection. We demonstrated that these cytokines can activate CD4+ T cells, the target cells for HIV infection. Furthermore, these five EC-associated cytokines could change expression levels of intrinsic resistance factors, or molecules inside the target cell that fight HIV infection. This study is significant in that it identified cytokines elevated in subjects with a good immune response against HIV and defined potential mechanisms as to how these cytokines could induce resistance to the virus in target cells

Bat Eyes Have Ultraviolet-Sensitive Cone Photoreceptors

Mammalian retinae have rod photoreceptors for night vision and cone photoreceptors for daylight and colour vision. For colour discrimination, most mammals possess two cone populations with two visual pigments (opsins) that have absorption maxima at short wavelengths (blue or ultraviolet light) and long wavelengths (green or red light). Microchiropteran bats, which use echolocation to navigate and forage in complete darkness, have long been considered to have pure rod retinae. Here we use opsin immunohistochemistry to show that two phyllostomid microbats, Glossophaga soricina and Carollia perspicillata, possess a significant population of cones and express two cone opsins, a shortwave-sensitive (S) opsin and a longwave-sensitive (L) opsin. A substantial population of cones expresses S opsin exclusively, whereas the other cones mostly coexpress L and S opsin. S opsin gene analysis suggests ultraviolet (UV, wavelengths <400 nm) sensitivity, and corneal electroretinogram recordings reveal an elevated sensitivity to UV light which is mediated by an S cone visual pigment. Therefore bats have retained the ancestral UV tuning of the S cone pigment. We conclude that bats have the prerequisite for daylight vision, dichromatic colour vision, and UV vision. For bats, the UV-sensitive cones may be advantageous for visual orientation at twilight, predator avoidance, and detection of UV-reflecting flowers for those that feed on nectar